Our proposed study is aimed at the development and validation of indirect tests for the detection of mechanical abnormalities of the small airways of the lung. The specific test under study is one which combines frequency dependence of resistance measurements with the utilization of gases of varying densities. Specific objectives toward this aim are: 1) development of the "two-gas" technique in humans and development of a technique for direct measurement of small airway resistance in dogs; 2) testing the validity, sensitivity and reproducibility of the technique in animal and human models of specific small airway abnormalities; and 3) application of the technique to specific patient populations with known or suspected small airway disease. In the past year we have accomplished the following: 1) the frequency dependence - two-gas technique has been automated and its reproducibility confirmed and we are now able to measure small airway resistance in the close-chested dog; 2) we have determined the relative importance of H1 and H2 receptors to central and peripheral airway resistance during histamine infusion in the dog; and 3) we have found that the two-gas-frequency dependence technique is highly sensitive to increases in small airway resistance in normal man, as determined via histamine infusion with simultaneous measurement of dynamic compliance and its frequency dependence.